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Thiophene-based monohelicene ( TS[7]H ), triple helicenes ( TT[7]H ), and hexapole helicenes ( TH[7]H ) were synthesized via oxidative photocyclization and cascade Suzuki/intramolecular cyclization as the crucial steps. The enantiomers of TS[7]H , TT[7]H-2 , and TH[7]H exhibited circularly polarized luminescence (CPL), and the luminescence dissymmetry factors ( g lum ) gradually increased from -5.1 × 10 -4 to -2.0 × 10 -3 with an increase in multiplicity from TS[7]H to TH[7]H . In addition, TS[7]H , TT[7]H , and TH[7]H displayed a second-level long afterglow at 77 K.

In this study, ultrafine linear nanostructured SiC with high wettability and large specific surface area were synthesized via the carbothermal reduction method. These nanowires were impregnated with Na 2 SO 4  ⋅ 10H 2 O, CaCl 2  ⋅ 6H 2 O, MgCl 2  ⋅ 6H2O, and CaMg 2 Cl 6  ⋅ 12H 2 O to obtain composite phase change materials (CPCMs), which demonstrated improved phase separation and significantly reduced supercooling. In particular, the supercooling degree of CaCl 2  ⋅ 6H 2 O was minimized to 0.1 °C. The SiC nanowires effectively prevented issues of dehydration and deliquescence in hydrated salts. The thermal storage capacities of the CPCMs exceeded 90 %, with Na 2 SO 4  ⋅ 10H 2 O and MgCl 2  ⋅ 6H 2 O reaching 107.10 % and 103.35 %, respectively. Furthermore, the CPCMs exhibited greater sensitivity to changes in temperature compared with the pure hydrated salt phase change materials (PCMs). These results indicate that ultra-fine SiC nanowires can act as a versatile carrier for hydrated salt PCMs at low and intermediate temperatures., (© 2024 Wiley-VCH GmbH.)

Purpose: To evaluate the clinical and retinal imaging features of Chinese patients with acute macular neuroretinopathy (AMN) associated with COVID-19., Design: A prospective observational study., Methods: Retinal imaging, including color fundus photography, near-infrared imaging (NIR), swept-source optical coherence tomography (SS-OCT), optical coherence tomography angiography (OCTA), and Humphrey perimetry, were conducted for each case., Results: All cases were included within the first three months following the pandemic outbreak. A total of 12 male patients (36.36 %) and 21 female patients (63.64 %) were prospectively recruited, and 29 cases (87.88 %) were bilaterally affected. The median interval between the onset of fever and the appearance of ocular symptoms was two days (range, 0.5-5.0 days). Apart from the outer retinal changes typical of AMN, changes in the inner retinal layers were observed, including intraretinal hemorrhage (8.06 %), cotton wool spots (9.68 %), and paracentral acute middle maculopathy (PAMM) (8.06 %). Smaller retinal inner nuclear layer hyperreflective speckles (RIHS) (41.94 %) were identified as a distinguishing feature from typical PAMM. Voids of vessel signals were found in the superficial (11.54 %), intermediate (82.69 %), and deep capillary plexus (98.08 %), and in the choriocapillaris (19.23 %) on OCTA. Humphrey perimetry illustrated central, paracentral, and peripheral scotomas. The occult lesions associated with AMN, PAMM, and some of the RIHS illustrated by OCT were visualized topographically and further confirmed by OCTA as perfusion defects., Conclusion: An increase in AMN cases correlated with the SARS-CoV-2 outbreak. Additional features, including widespread inner retinal perfusion deficits, were observed and may serve as potential biomarkers for systemic microcirculation dysregulation in COVID-19., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the preference of primary HCWs and residents on vaccination consultation in community health services to provide evidence for vaccine hesitancy intervention strategies., Methods: A discrete choice model (DCM) was constructed to evaluate the preference difference between primary HCWs and residents on vaccination consultation in community health services in China during May-July 2022., Results: A total of 282 residents and 204 HCWs were enrolled in this study. The residents preferred consulting with an HCW-led approach (β = 2.168), with specialized content (β = 0.954), and accompanied by telephone follow-up (β = 1.552). In contrast, the HCWs preferred face-to-face consultation (β = 0.540) with an HCW-led approach (β = 0.458) and specialized content (β = 0.409), accompanied by telephone follow-up (β = 0.831). College residents and residents with underlying self-reported disease may be near-critically inclined to choose traditional consultation (an offline, face-to-face consultation with standardized content and more prolonged duration) rather than a new-media consulting group (an online consultation with specialized content within 5 min). Urban HCWs preferred long-term consultation groups (the resident-led offline consultation with follow-up lasting more than 5 min). In contrast, rural HCWs preferred efficient consultation (the HCW-led, short-duration, standardized offline consultation mode)., Conclusion: The selection preference for vaccine consultation reveals a gap between providers and demanders, with different groups exhibiting distinct preferences. Identifying these targeted gaps can help design more acceptable and efficient interventions, increasing their likelihood of success and leading to better resource allocation for policymakers to develop targeted vaccination policies.

Objective: To estimate whether genetically proxied periodontitis causally impacts the brain cortical structure using Mendelian randomization (MR)., Background: Periodontitis is one of the most prevalent inflammatory conditions globally, and emerging evidence has indicated its influences on distal organs, including the brain, whose disorders are always accompanied by magnetic resonance imaging (MRI)-identified brain cortical changes. However, to date, no available evidence has revealed the association between periodontitis and brain cortical structures., Methods: The instrumental variables (IVs) were adopted from previous genome-wide association study (GWAS) studies and meta-analyses of GWAS studies of periodontitis from 1844 to 5266 cases and 8255 to 12 515 controls. IVs were linked to GWAS summary data of 51 665 patients from the ENIGMA Consortium, assessing the impacts of genetically proxied periodontitis on the surficial area (SA) or the cortical thickness (TH) of the global and 34 MRI-identified functional regions of the brain. Inverse-variance weighted was used as the primary estimate; the MR pleiotropy residual sum and outlier (MR-PRESSO), the MR-Egger intercept test, and leave-one-out analyses were used to examine the potential horizontal pleiotropy., Results: Genetically proxied periodontitis affects the SA of the medial orbitofrontal cortex, the lateral orbitofrontal cortex, the inferior temporal cortex, the entorhinal cortex, and the temporal pole, as well as the TH of the entorhinal. No pleiotropy was detected., Conclusions: Periodontitis causally influences the brain cortical structures, implying the existence of a periodontal tissue-brain axis., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The object detection of the substation is the key to ensuring the safety and reliable operation of the substation. The traditional image detection algorithms use the corresponding texture features of single-class objects and would not handle other different class objects easily. The object detection algorithm based on deep networks has generalization, and its sizeable complex backbone limits the application in the substation monitoring terminals with weak computing power. This article proposes a multitargets joint training lightweight model. The proposed model uses the feature maps of the complex model and the labels of objects in images as training multitargets. The feature maps have deeper feature information, and the feature maps of complex networks have higher information entropy than lightweight networks have. This article proposes the heat pixels method to improve the adequate object information because of the imbalance of the proportion between the foreground and the background. The heat pixels method is designed as a kind of reverse network calculation and reflects the object's position to the pixels of the feature maps. The temperature of the pixels indicates the probability of the existence of the objects in the locations. Three different lightweight networks use the complex model feature maps and the traditional tags as the training multitargets. The public dataset VOC and the substation equipment dataset are adopted in the experiments. The experimental results demonstrate that the proposed model can effectively improve object detection accuracy and reduce the time-consuming and calculation amount.

Objectives: Dental caries is one of the most prevalent oral diseases and causes of tooth loss. Cross-sectional studies observed epidemiological associations between dental caries and brain degeneration disorders, while it is unknown whether dental caries causally affect the cerebral structures. This study tested whether genetically proxied DMFS (the sum of Decayed, Missing, and Filled tooth Surfaces) causally impacts the brain cortical structure using Mendelian randomization (MR)., Methods: The summary-level GWAS meta-analysis data from the GLIDE consortium were used for DMFS, including 26,792 participants. ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) consortium GWAS summary data of 51,665 patients were used for brain structure. This study estimated the causal effects of DMFS on the surface area (SA) and thickness (TH) of the global cortex and functional cortical regions accessed by magnetic resonance imaging (MRI). Inverse-variance weighted (IVW) was used as the primary estimate, the MR pleiotropy residual sum and outlier (MR-PRESSO), the MR-Egger intercept test, and leave-one-out analyses were used to examine the potential horizontal pleiotropy., Results: Genetically proxied DMFS decreases the TH of the banks of the superior temporal sulcus (BANSSTS) with or without global weighted (weighted, β = - 0.0277 mm, 95% CI: - 0.0470 mm to - 0.0085 mm, P = 0.0047; unweighted, β = - 0.0311 mm, 95% CI: - 0.0609 mm to - 0.0012 mm, P = 0.0412). The causal associations were robust in various sensitivity analyses., Conclusions: Dental caries causally decrease the cerebral cortical thickness of the BANKSSTS, a cerebral cortical region crucial for language-related functions, and is the most affected brain region in Alzheimer's disease. This investigation provides the first evidence that dental caries causally affects brain structure, proving the existence of teeth-brain axes. This study also suggested that clinicians should highlight the causal effects of dental caries on brain disorders during the diagnosis and treatments, the cortical thickness of BANKSSTS is a promising diagnostic measurement for dental caries-related brain degeneration., (© 2024. The Author(s).)

Maleimide chemistry is widely used in antibody-drug conjugate (ADC) generation to connect drugs to antibodies through a succinimide linker. The resulting ADC is prone to payload loss via a reverse Michael reaction, leading to premature drug release in vivo . Complete succinimide hydrolysis is an effective strategy to overcome the instability of ADC. However, we discovered through previous work that hydrolysed succinimide rings can close again in a liquid formulation during storage and under thermal stress conditions. In this work, a set of maleimide linkers with hydrolysis-prone groups were designed. The corresponding ADCs were prepared and subjected to thermal stress conditions. The extent of succinimide hydrolysis and drug release was measured, and ADC properties such as SEC, DAR, pI and clog  P of linkers were calculated. Our results demonstrated that even though all these groups increased the hydrolysis rate, they have different impacts on maintaining the hydrolysed succinimide ring in an open conformation and ADC stability in a liquid formulation., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Side chains of natural occurring amino acids vary greatly in terms of charge state, polarity, size and hydrophobicity. Using a linear synthetic route, two amino acids were sequentially coupled to a potent glucocorticoid receptor modulator (GRM) to afford a library of dipeptide-GRM linker payloads with a range of in silico properties. The linker payloads were conjugated to a mouse anti-TNF antibody through interchain disulfide Cys. Impact of various dipeptide linkers on ADC physical properties, including solubility, hydrophobicity, and aggregation were evaluated and the in silico properties pI, Log  P and tPSA of the linker drugs used to correlate with these properties. ADCs were screened in a GRE luciferase reporter assay to compare their in vitro efficacy. Data identified Ala-Ala as a superior dipeptide linker that allowed a maximum drug load of 10 while affording ADCs with low aggregation., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Chimeric antigen receptor T cell (CAR-T) therapies show considerable clinical efficacy in patients with B cell malignancies, but their efficacy is limited in patients with T cell acute lymphoblastic leukemia (T-ALL). CD5 is expressed on ∼85 % of malignant T cells, and CD5-targeting CAR-T cells can exhibit potent antitumor activity against T-ALL. However, optimization of CAR costimulatory endo-, hinge, and transmembrane domains could further increase their expansion and persistence, thereby enhancing their efficacy following exposure to tumor cells. Here we designed CD5-specific CARs with different molecular structures to generate CAR-T cells and investigated their anti-tumor efficacy in vitro and in vivo. CD5 CARs with a 4-1BB costimulatory domain (BB.z) or a CD28 costimulatory domain (28.z) exhibited specific cytotoxicity against CD5 + malignant cells in vitro. However, both failed to prolong the survival of T-ALL xenograft mice. Subsequently, we substituted the 28.z CAR hinge region with C H 2C H 3, which enhanced the ability of C H 2C H 3-CD5 CAR-T cells to specifically eradicate T-ALL cells in vitro and in vivo. Furthermore, patient-derived C H 2C H 3-CD5 CAR-T cells were generated which showed a marked killing effect of CD5-positive acute T-ALL cells in vitro. The anti-tumor activity of CD5 CAR-T cells with a CD28 co-stimulation domain and C H 2C H 3 hinge region was superior to those with BB.z and 28.z domains. These preclinical data provided new insights into the factors dictating efficacy in T-ALL treatment with CAR-T cells and hold promise for clinical translation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Systemic inflammatory response syndrome (SIRS), at least in part driven by necroptosis, is characterized by life-threatening multiple organ failure. Blocking the progression of SIRS and consequent multiple organ dysfunction is challenging. Receptor-interacting serine/threonine protein kinase 1 (RIPK1) is an important cell death and inflammatory mediator, making it a potential treatment target in several diseases. Here, using a drug repurposing approach, we show that inhibiting RIPK1 is also an effective treatment for SIRS. We performed cell-based high-throughput drug screening of an US Food and Drug Administration (FDA)-approved drug library that contains 1953 drugs to identify effective inhibitors of necroptotic cell death by SYTOX green staining. Dose-response validation of the top candidate, quizartinib, was conducted in two cell lines of HT-22 and MEFs. The effect of quizartinib on necroptosis-related proteins was evaluated using western blotting, immunoprecipitation, and an in vitro RIPK1 kinase assay. The in vivo effects of quizartinib were assessed in a murine tumor necrosis factor α (TNFα)-induced SIRS model. High-throughput screening identified quizartinib as the top "hit" in the compound library that rescued cells from necroptosis in vitro. Quizartinib inhibited necroptosis by directly inhibiting RIPK1 kinase activity and blocking downstream complex IIb formation. Furthermore, quizartinib protected mice against TNFα-induced SIRS. Quizartinib, as an FDA-approved drug with proven safety and efficacy, was repurposed for targeted inhibition of RIPK1. This work provides essential preclinical data for transferring quizartinib to the treatment of RIPK1-dependent necroptosis-induced inflammatory diseases, including SIRS., (© 2023 Federation of American Societies for Experimental Biology.)

High-risk neuroblastoma exhibits transcriptional activation of the mevalonate pathway that produces cholesterol and nonsterol isoprenoids. A better understanding of how this metabolic reprogramming contributes to neuroblastoma development could help identify potential prevention and treatment strategies. Here, we report that both the cholesterol and nonsterol geranylgeranyl-pyrophosphate branches of the mevalonate pathway are critical to sustain neuroblastoma cell growth. Blocking the mevalonate pathway by simvastatin, a cholesterol-lowering drug, impeded neuroblastoma growth in neuroblastoma cell line xenograft, patient-derived xenograft (PDX), and TH-MYCN transgenic mouse models. Transcriptional profiling revealed that the mevalonate pathway was required to maintain the FOXM1-mediated transcriptional program that drives mitosis. High FOXM1 expression contributed to statin resistance and led to a therapeutic vulnerability to the combination of simvastatin and FOXM1 inhibition. Furthermore, caffeine synergized with simvastatin to inhibit the growth of neuroblastoma cells and PDX tumors by blocking statin-induced feedback activation of the mevalonate pathway. This function of caffeine depended on its activity as an adenosine receptor antagonist, and the A2A adenosine receptor antagonist istradefylline, an add-on drug for Parkinson's disease, could recapitulate the synergistic effect of caffeine with simvastatin. This study reveals that the FOXM1-mediated mitotic program is a molecular statin target in cancer and identifies classes of agents for maximizing the therapeutic efficacy of statins, with implications for treatment of high-risk neuroblastoma., Significance: Caffeine treatment and FOXM1 inhibition can both enhance the antitumor effect of statins by blocking the molecular and metabolic processes that confer statin resistance, indicating potential combination therapeutic strategies for neuroblastoma. See related commentary by Stouth et al., p. 2091., (©2023 The Authors; Published by the American Association for Cancer Research.)

Leonurine (Leo) is a natural alkaloid isolated from the herb Leonurus japonicus Houtt. (Leonuri) that has been shown to inhibit oxidative stress and inflammation. However, the role and mechanism of Leo in acetaminophen (APAP)-induced acute liver injury (ALI) remain unknown. In this study, we investigated the protective effect of Leo against APAP-induced ALI and elucidated the molecular mechanism. Here, we showed that the damage to mouse primary hepatocytes (MPHs) induced by APAP was attenuated by treatment with Leo, which promoted proliferation and inhibited oxidative stress injury, and Leo significantly improved APAP-induced ALI in mice. Leo could protect against APAP-induced ALI by reducing serum aspartate aminotransferase (AST) and alanine transaminase (ALT) levels, hepatic histopathological damage, liver cell necrosis, inflammation, and oxidative stress-induced damage in vivo and in vitro. Moreover, the results indicated that Leo relieved APAP-induced liver cell necrosis by reducing the expression of Bax and cleaved caspase-3 and increasing Bcl-2 expression. Leo alleviated APAP-induced oxidative stress-induced damage by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway, which facilitated Nrf2 nuclear translocation and upregulated oxidative stress-related protein expression in liver tissues. Moreover, the results suggested that APAP-induced inflammation in the liver was suppressed by Leo by suppressing the Toll-like receptor 4 (TLR4) and NLR family pyrin domain containing 3 (NLRP3) pathways. In addition, Leo facilitated the activation of the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway in the liver tissue of ALI mice. Network pharmacology, molecular docking, and western blotting showed that PI3K was a potential target of Leo in the treatment of ALI. Molecular docking and cellular thermal shift assay (CETSA) indicated that Leo could stably bind to the PI3K protein. In conclusion, Leo attenuated ALI, and reversed liver cell necrosis, the inflammatory response and oxidative stress-induced damage by regulating the PI3K/AKT signaling pathway., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

After tissue damage, a series of molecular and cellular events are initiated to promote tissue repair and regeneration to restore its original structure and function. These events include inter-cell communication, cell proliferation, cell migration, extracellular matrix differentiation, and other critical biological processes. Glycosylation is the crucial conservative and universal post-translational modification in all eukaryotic cells [1], with influential roles in intercellular recognition, regulation, signaling, immune response, cellular transformation, and disease development. Studies have shown that abnormally glycosylation of proteins is a well-recognized feature of cancer cells, and specific glycan structures are considered markers of tumor development. There are many studies on gene expression and regulation during tissue repair and regeneration. Still, there needs to be more knowledge of complex carbohydrates' effects on tissue repair and regeneration, such as glycosylation. Here, we present a review of studies investigating protein glycosylation in the tissue repair and regeneration process., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

(1) Background: To explore the influencing factors of human papillomavirus (HPV) vaccination among mothers and daughters so as to provide evidence and strategies for improving the HPV vaccination rate of 9-18-years-old girls. (2) A questionnaire survey was conducted among the mothers of 9-18-year-old girls from June to August 2022. The participants were divided into the mother and daughter vaccinated group (M1D1), the mother-only vaccinated group (M1D0), and the unvaccinated group (M0D0). Univariate tests, the logistic regression model, and the Health Belief Model (HBM) were employed to explore the influencing factors. (3) Results: A total of 3004 valid questionnaires were collected. According to the regions, Totally 102, 204, and 408 mothers and daughters were selected from the M1D1, M1D0, and M0D0 groups, respectively. The mother having given her daughter sex education (OR = 3.64; 95%CI 1.70, 7.80), the mother's high perception of disease severity (OR = 1.79; 95%CI 1.02, 3.17), and the mother's high level of trust in formal information (OR = 2.18; 95%CI 1.26, 3.78) were all protective factors for both the mother and her daughter's vaccination. The mother's rural residence (OR = 0.51; 95%CI 0.28, 0.92) was a risk factor for vaccination of both mother and daughter. The mother's education of high school or above (OR = 2.12; 95%CI 1.06, 4.22), the mother's high level of HPV and HPV vaccine knowledge (OR = 1.72; 95%CI 1.14, 2.58), and the mother's high level of trust in formal information (OR = 1.72; 95%CI 1.15, 2.57) were protective factors of mother-only vaccination. The older the mother (OR = 0.95; 95%CI 0.91, 0.99) was classed as a risk factor for mother-only vaccination. "Waiting until the daughters are older to receive the 9-valent vaccine" is the main reason why the daughters of M1D0 and M0D0 are not vaccinated". (4) Chinese mothers had a high willingness to vaccinate their daughters with the HPV vaccine. The higher education level of the mother, giving sex education to the daughter, the older ages of mothers and daughters, the mother's high level of HPV and HPV vaccine knowledge, a high level of perception of the disease severity, and a high level of trust in formal information were promoting factors of HPV vaccination for mother and daughter, and rural residence was a risk factor to vaccination. To promote HPV vaccination in girls from 9-18 years old, communities could provide health education to rural mothers with low education levels; the government could advocate for HPV vaccination through issuing policy documents; and doctors and the CDC could popularize the optimal age for HPV vaccination to encourage mothers to vaccinate their daughters at the age of 9-14 years old.

Receptor-interacting protein kinase 1 (RIPK1) has emerged as a key regulator of cell death and inflammation, which are implicated in the pathogenesis of many inflammatory and degenerative diseases. RIPK1 is therefore a putative therapeutic target in many of these diseases. However, no pharmacological inhibitor of RIPK1-mediated cell death is currently in clinical use. Recognizing that a repurposed drug has an expedited clinical development pipeline, here we performed a high-throughput drug screen of Food and Drug Administration (FDA)-approved compounds and identified a novel use for crizotinib as an inhibitor of RIPK1-dependent cell death. Furthermore, crizotinib rescued TNF-α-induced death in mice with systemic inflammatory response syndrome. RIPK1 kinase activity was directly inhibited by crizotinib. These findings identify a new use for an established compound and are expected to accelerate drug development for RIPK1-spectrum disorders., (© The Author(s) 2022. Published by Oxford University Press on behalf of The Japanese Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The goal of this study was to examine the role of sodium butyrate in preserving the intestinal mucosal barrier and reducing hyperuricemia (HUA)., Methods: First, we established a mouse model of HUA via intraperitoneal injection of potassium oxonate together with a yeast-rich diet to detect the levels of serum uric acid (UA) and fecal short-chain fatty acids (SCFAs). Then, in vitro, different concentrations of UA and sodium butyrate (NaB) were used to treat LS174T and Caco2 cells. The effects of UA and NaB on the gut barrier were determined based on the expression levels of MUC2, ZO-1, and Occludin.Finally, C57BL/6 mice were used to model HUA, and these mice were administered 200 mg·kg -1 ·d -1 NaB by gavage to counter the HUA. The effect of NaB on HUA in the intestinal tract was elucidated by determining serum UA levels, inflammatory parameters, epithelial barrier integrity, and via histological analysis., Results: The data showed that the content of fecal SCFAs in HUA mice decreased. Additionally, in LS174T and Caco2 cells, NaB reversed the decrease of ZO-1, Occludin, and MUC2 protein expression caused by high UA levels. Furthermore, NaB decreased serum UA of HUA mice, and reversed both the decreased expression of MUC2, ZO-1, Occludin, and ABCG2 proteins and the increased level of inflammatory factors in the intestinal tissues of these mice., Conclusion: The HUA mouse model showed intestinal barrier damage. NaB protected the intestinal barrier of HUA mice and reduced the serum UA level., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Musculoskeletal disorders are the second leading cause of disability worldwide, posing a huge global burden to the public sanitation system. Currently, tissue engineering-based approaches act as effective strategies, which are, however, challenging in limited application scenarios. Mussel-based biomimetic materials, exhibit numerous unique properties such as intense adhesion, biocompatibility, moisture resistance, and injectability, to name only a few, and have attracted extensive research interest. In particular, featuring state-of-the-art properties, mussel-inspired biomaterials have been widely explored in innumerable musculoskeletal disorder treatments including osteochondral defects, osteosarcoma, osteoarthritis, ligament rupture, and osteoporosis. Nevertheless, a comprehensive and timely discussion of their applications in musculoskeletal disorders is insufficient. In this review, we emphasize on (1) the main categories and characteristics of mussel foot proteins and their fundamental mechanisms for the spectacular adhesion in mussels; (2) the diverse synthetic methods and modification of various polymers; and (3) the emerging applications of mussel-biomimetic materials, the future perspectives, and challenges, especially in the area of musculoskeletal disorder. We envision that this review will provide a unique and insightful perspective to improve the development of a new generation of mussel biomimetic strategies., Competing Interests: The authors declare no conflicts of interest in this work., (© 2023 Yu et al.)

Purpose: To observe the characteristics of highly myopic macular holes (HMMHs) with macular retinoschisis (MRS) by optical coherence tomography (OCT) and explore the possible relationship between HMMHs and different types of MRS., Methods: We consecutively reviewed the clinical data and OCT images of the patients with HMMHs from June 2015 to February 2021. Then we picked eyes with MRS from these HMMHs for analysis. The minimum linear diameter (MLD), basal diameter (BD), and height (H) of HMMHs were measured. HMMHs were grouped according to the extent or layer involvement of the concomitant MRS and the characteristics were compared among groups. The impact of MRS on the MLD of macular hole was analyzed with multivariable linear regression., Results: We included 127 patients with MRS from 168 HMMHs (75.5%) for analysis. According to the different classification systems, the most frequent type of MRS in HMMHs was S3 (foveal but not entire macular area MRS) (62.2%) and both inner- and outer- (I/O-MRS) involved types. In our study, HMMHs with more extensive MRS had larger MLD, larger BD, larger H, and poorer best-corrected visual acuity (BCVA). Meanwhile, HMMHs with outer layer-involved MRS (outer MRS and I/O-MRS) had larger BD than HMMH with only inner layer-involved MRS. (All P < 0.05) Multivariable linear regression further illustrated only the extent of MRS was significantly associated with the MLD of HMMH, while there was no significant correlation between the involved retinal layers and the MLD of HMMH., Conclusion: HMMH with MRS presented as a predominant type in HMMHs. The MRS was always with a relatively large extent and involved both inner and outer layers. MLD of HMMH was mainly affected by the extent of MRS., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Using a convergent synthetic route to enable multiple points of diversity, a series of glucocorticoid receptor modulators (GRM) were profiled for potency, selectivity, and drug-like properties in vitro . Despite covering a large range of diversity, profiling the nonconjugated small molecule was suboptimal and they were conjugated to a mouse antitumor necrosis factor (TNF) antibody using the MP-Ala-Ala linker. Screening of the resulting antibody drug conjugates (ADCs) provided a better assessment of efficacy and physical properties, reinforcing the need to conduct structure-activity relationship studies on the complete ADC. DAR4 ADCs were screened in an acute mouse contact hypersensitivity model measuring biomarkers to ensure a sufficient therapeutic window. In a chronic mouse arthritis model, mouse anti-TNF GRM ADCs were efficacious after a single dose of 10 mg/kg i.p. for over 30 days. Data on the unconjugated payloads and mouse surrogate anti-TNF ADCs identified payload 17 which was conjugated to a human anti-TNF antibody and advanced to the clinic as ABBV-3373.

The short-chain hydrocarbon polymerization-catalyzed synthetic fuel technology has great development potential in the fields of energy storage and renewable energy. Modeling and optimization of a short-chain hydrocarbon polymerization-catalyzed synthetic fuel process involving mixers, compressors, heat exchangers, reactors, and separators are performed through finite-time thermodynamics. Under the given conditions of the heat source temperature of the heat exchanger and the reactor, the optimal performance of the process is solved by taking the mole fraction of components, pressure, and molar flow as the optimization variables, and taking the minimum entropy generation rate (MEGR) of the process as the optimization objective. The results show that the entropy generation rate of the optimized reaction process is reduced by 48.81% compared to the reference process; among them, the component mole fraction is the most obvious optimization variable. The research results have certain theoretical guiding significance for the selection of the operation parameters of the short-chain hydrocarbon polymerization-catalyzed synthetic fuel process.

Objective: To analyze and compare the associations of hyperuricemia (HUA) with obesity, triglyceride-glucose (TyG), and its derivatives in college students. To provide early guidance on risk predictors of HUA in college students., Methods: This study was a cross-sectional survey including 23,411 participants (age: 17-20 years). Investigators conducted face-to-face interview surveys and physical examinations. Automated biochemical methods were used to detect biochemical indicators such as serum uric acid (UA). Calculation of obesity, TyG, and their derivatives indices were performed. Logistic regression was used to analyze the relationship between different indexes and hyperuricemia. OR value and 95% CI were also calculated. ROC curve was used for assessing the predictive ability of different indices of hyperuricemia., Results: After adjusting for age, SBP, DBP, ALT, AST, TC, BUN, and CREA, multivariate logistic regression showed that the OR value of LAP in the obesity index was higher, especially in women (male OR: 4.347, 95%CI: 3.807, 4.964; female OR: 4.672, 95%CI: 3.800, 5.744). The other three quartiles of TyG derivatives were highly associated with hyperuricemia in men and women compared with the top quartile (all P< 0.05). The risk of hyperuricemia increased with an increase in quartiles. For college students, all indicators could distinguish the presence of hyperuricemia. For men, the area under the curve (AUC) of TyG-WC was the largest (AUC: 0.694; 95%CI: 0.684-0.704; P<0.05), according to the Maximum Youden index 0.290 with cut point value 477.853. In women, TyG-BMI showed a maximum AUC value of 0.702 (95%CI: 0.685-0.719; P<0.05), according to the maximum Youden index of 0.317 with cut point value 132.446. The TyG-WC, TyG-WHtR, TyG-LAP, and LAP indices also had relatively high AUC., Conclusion: In clinical practice, LAP, TYG, and their related derivatives may be used as sensitive indicators for HUA prediction in college students., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhou, Yu, Zhang, Ma, Wang, Yang, Cheng, Liu, Sun and Chen.)

Tissue regeneration after body injury has always been a complex problem to resolve for mammals. In adult mammals, the repair process after tissue injury is often accompanied by continuous and extensive fibrosis, which leads to scars. This process has been shown to severely hinder regeneration. Macrophages, as widely distributed innate immune cells, not only play an important role in various pathological processes, but also participate in the repair process before tissue regeneration and coordinate the regeneration process after repair. This review will discuss the various forms and indispensability of macrophages involved in repair and regeneration, and how macrophages play a role in the repair and regeneration of different tissues., Competing Interests: The authors declare there are no competing interests., (©2022 Yu et al.)

Background: Asprosin (ASP) is a recently discovered adipocyte factor that participates in glucose metabolism and inflammatory reactions. Recent findings suggest that it may be involved in the regulation of sex hormone secretion in the hypothalamic-pituitary-gonad (HPG) axis, but no studies have been reported in related populations. The purpose of this study was to evaluate the changes in serum ASP levels in healthy men and obese men, as well as before and after exercise weight loss, and to investigate male hypogonadism, insulin resistance, inflammatory response, and relationships induced by ASP and obesity. Methods: Thirty-eight young male volunteers were recruited and divided into a normal group ( n = 20) and an obese group ( n = 18) according to their body mass index. Fourteen of the obese men underwent a 14-week exercise and diet intervention (first 8 weeks of aerobic exercise at 60%-70% HR max for 30-50 min/4 days a week). Beginning at week 9, the intensity was increased to 75% HR max . Participants in the obese groups maintained a calorie-restricted diet throughout the study period. Results: Serum ASP levels in the obese group were significantly higher than those in the normal group, and serum gonadotropin-releasing hormone (GnRh), luteinizing hormone (LH), and testosterone (T) levels were decreased. After 14 weeks of exercise and diet intervention, serum ASP decreased significantly, the levels of body weight, lean body weight, body fat rate, fasting insulin (FINS), homeostatic model assessment for insulin resistance, TNF-α, IL-6, and IL-1β decreased significantly, and the serum GnRH, LH, and T levels increased significantly. ASP was positively correlated with body weight, body fat percentage, FINS, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β and negatively correlated with relative lean body weight and serum LH and T levels. Conclusion: The serum ASP levels were increased in obese men compared with those of normal weight individuals, resulting in a chronic inflammatory reaction, high serum insulin, and HPG axis injury. Fourteen weeks of exercise and diet intervention effectively alleviated this phenomenon. It has been speculated that ASP might regulate male reproductive function by regulating the inflammatory response and insulin sensitivity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yao, Song, Yu, Cheng, Lu, Li, Yang, Tang and Yi.)

Exosomes are widely involved in a variety of physiological and pathological processes. These important roles are also hidden in the physiological processes related to bone. Chondrocytes, osteoblasts, synovial fibroblasts, and bone marrow mesenchymal stem cells produce and secrete exosomes, thereby affecting the biology process of target cells. Furthermore, in the primary pathogenesis of osteoarthrosis induced by steroid hormones, mainly involve glucocorticoid (GC), the exosomes have also widely participated. Therefore, exosomes may also play an important role in glucocorticoid-induced osteoarthrosis and serve as a promising treatment for early intervention of osteoarthrosis in addition to playing a regulatory role in malignant tumors. This review summarizes the previous results on this direction, systematically combs the role and therapeutic potential of exosomes in GC-induced osteoarthrosis, discusses the potential role of exosomes in the treatment and prevention of GC-induced osteoarthrosis, and reveals the current challenges we confronted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Lv, Cheng, Yu, Chen, Gan, Li, Zhao, Yang and Zhang.)

Aims: Bladder outlet obstruction (BOO) and the consequent low contractility of detrusor are the leading causes of voiding dysfunction. In this study, we aimed to evaluate the pharmacological activity of astragaloside IV (AS-IV), an antioxidant biomolecule that possess beneficial effect in many organs, on detrusor contractility and bladder wall remodeling process., Methods: Partial BOO (pBOO) was created by urethral occlusion in female rats, followed by oral gavage of different dose of AS-IV or vehicle. Cystometric evaluation and contractility test were performed. Bladder wall sections were used in morphology staining, and bladder tissue lysate was used for ELISA assay. Primary smooth muscle cells (SMCs) derived from detrusor were used for mechanism studies., Results: Seven weeks after pBOO, the bladder compensatory enlarged, and the contractility in response to electrical or chemical stimuli was reduced, while AS-IV treatment reversed this effect dose-dependently. AS-IV also showed beneficial effect on reversing the bladder wall remodeling process, as well as reducing ROS level. In mechanism study, AS-IV activated mitophagy and alleviated oxidative stress via an AMPK-dependent pathway., Conclusion: Out data suggested that AS-IV enhanced the contractility of detrusor and protected the bladder from obstruction induced damage, via enhancing the mitophagy and restoring mitochondria function trough an AMPK-dependent way., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2022 Xiaoyu Zhu et al.)

The use of olefin oligomerization in the synthesis of liquid fuel has broad application prospects in military and civil fields. Here, based on finite time thermodynamics (FTT), an ethylene oligomerization chemical process (EOCP) model with a constant temperature heat source outside the heat exchanger and reactor pipes was established. The process was first optimized with the minimum specific entropy generation rate (SEGR) as the optimization objective, then multi-objective optimization was further performed by utilizing the NSGA-II algorithm with the minimization of the entropy generation rate (EGR) and the maximization of the C 10 H 20 yield as the optimization objectives. The results showed that the point of the minimum EGR was the same as that of SEGR in the Pareto optimal frontier. The solution obtained using the Shannon entropy decision method had the lowest deviation index, the C 10 H 20 yield was reduced by 49.46% compared with the point of reference and the EGR and SEGR were reduced by 59.01% and 18.88%, respectively.

Glucocorticoid receptor modulators (GRM) are the first-line treatment for many immune diseases, but unwanted side effects restrict chronic dosing. However, targeted delivery of a GRM payload via an immunology antibody-drug conjugate (iADC) may deliver significant efficacy at doses that do not lead to unwanted side effects. We initiated our α-TNF-GRM ADC project focusing on identifying the optimal payload and a linker that afforded stable attachment to both the payload and antibody, resulting in the identification of the synthetically accessible maleimide-Gly-Ala-Ala linker. DAR 4 purified ADCs were shown to be more efficacious in a mouse contact hypersensitivity model than the parent α-TNF antibody. Analysis of P1NP and corticosterone biomarkers showed there was a sufficient therapeutic window between efficacy and unwanted effects. In a chronic mouse arthritis model, α-TNF-GRM ADCs were more efficacious than both the parent α-TNF mAb and an isotype control bearing the same GRM payload.

The function of long non-coding RNA LHFPL3 antisense RNA 1 (LHFPL3-AS1) in cancer progression has been studied, while its role in nasopharyngeal carcinoma (NPC) remains unclear. This study aims to unravel the effects of LHFPL3-AS1 on NPC progression via microRNA (miR)-143-5p/homeobox A6 (HOXA6) axis. NPC tissues were collected and NPC cells were cultured. NPC cells were subjected to radiation therapy to construct the radiation therapy resistance NPC cell line. The levels of LHFPL3-AS1, miR-143-5p and HOXA6 in NPC cells and tissues were examined. LHFPL3-AS1, miR-143-5p or HOXA6 expression was changed and then transfected into radiation-resistant NPC cells to detect cell proliferation, colony formation, migration, invasion and cell apoptosis in vitro . The tumorigenesis in nude mice in vivo was conducted to detect tumor growth. The targeting relations among LHFPL3-AS1, miR-143-5p and HOXA6 were validated. It was discovered that LHFPL3-AS1 and HOXA6 expression was elevated while the miR-143-5p level was depleted in radiation-resistant NPC cells and NPC tissues. The silenced LHFPL3-AS1 or augmented miR-143-5p repressed the proliferation, colony formation, migration and invasion of radiation-resistant NPC cells, while accelerated cell apoptosis in vitro . Silenced LHFPL3-AS1 hindered tumor growth in vivo . MiR-143-5p deletion reversed the effects of reduced LHFPL3-AS1; while HOXA6 upregulation reversed the effects of enriched miR-143-5p. LHFPL3-AS1 sponged miR-143-5p that targeted HOXA6. It is concluded that the down-regulated LHFPL3-AS1 retards the development of radiation-resistant NPC cells via sponging miR-143-5p to modulate HOXA6. This study reveals novel therapeutic targets for NPC treatment.

Introduction: Becker muscular dystrophy (BMD) is a genetic and progressive neuromuscular disease caused by mutations in the dystrophin gene with no available cure. A case report and comprehensive review of BMD cases aim to provide important clues for early diagnosis and implications for clinical practice. Genes and pathways identified from microarray data of muscle samples from patients with BMD help uncover the potential mechanism and provide novel therapeutic targets for dystrophin-deficient muscular dystrophies., Methods: We describe a BMD family with a 10-year-old boy as the proband and reviewed BMD cases from PubMed. Datasets from the Gene Expression Omnibus database were downloaded and integrated with the online software., Results: The systematic review revealed the clinical manifestations and mutation points of the dystrophin gene. Gene ontology analysis showed that extracellular matrix organization and extracellular structure organization with enrichment of upregulated genes coexist in three datasets. We present the first report of TUBA1A involvement in the development of BMD/Duchenne muscular dystrophy (DMD)., Discussion: This study provides important implications for clinical practice, uncovering the potential mechanism of the progress of BMD/DMD, and provided new therapeutic targets., (© 2021. Fondazione Società Italiana di Neurologia.)

The prognostic significance of miR-24 in tumors has not been determined. Therefore, we conducted a meta-analysis to systematically assess the correlation between miR-24 and its prognostic value in cancers PubMed, EMBASE, and Web of Science databases were used to search relevant articles (up to 1 October 2020). Studies that evaluated the prognostic value of miR-24 in tumors were included. The hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CI) were used to evaluate survival outcomes and clinical characteristics. All data analyses were implemented using STATA 12.0 software. A total of 17 studies from 15 articles involving 1705 patients were collected for the meta-analysis. The pooled analysis revealed that elevated miR-24 expression was obviously associated with poor overall survival (OS) (HR = 1.66, 95% CI: 1.20-2.31). Furthermore, we also found that elevated miR-24 expression was positively correlated with tumor size (large or small) and tumor stage (III-IV vs I-II). Elevated miR-24 expression indicates poor prognosis and may be a promising prognostic marker in different cancers. Our findings needed to be verified through further investigations. [Figure: see text].

Metabolic reprogramming is an integral part of the growth-promoting program driven by the MYC family of oncogenes. However, this reprogramming also imposes metabolic dependencies that could be exploited therapeutically. Here we report that the pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (DHODH) is an attractive therapeutic target for MYCN-amplified neuroblastoma, a childhood cancer with poor prognosis. Gene expression profiling and metabolomic analysis reveal that MYCN promotes pyrimidine nucleotide production by transcriptional upregulation of DHODH and other enzymes of the pyrimidine-synthesis pathway. Genetic and pharmacological inhibition of DHODH suppresses the proliferation and tumorigenicity of MYCN-amplified neuroblastoma cell lines. Furthermore, we obtain evidence suggesting that serum uridine is a key factor in determining the efficacy of therapeutic agents that target DHODH. In the presence of physiological concentrations of uridine, neuroblastoma cell lines are highly resistant to DHODH inhibition. This uridine-dependent resistance to DHODH inhibitors can be abrogated by dipyridamole, an FDA-approved drug that blocks nucleoside transport. Importantly, dipyridamole synergizes with DHODH inhibition to suppress neuroblastoma growth in animal models. These findings suggest that a combination of targeting DHODH and nucleoside transport is a promising strategy to overcome intrinsic resistance to DHODH-based cancer therapeutics., (© 2021. The Author(s).)

Background: Numbers of studies have reported that the expression of aldo-keto reductase family 1 member B10 (AKR1B10) is abnormal in digestive system cancers, and could be used as a prognostic biomarker. However, the results are argued. Therefore, we conduct a meta-analysis to comprehensively evaluate the prognostic value of high AKR1B10 expression for overall survival (OS), disease specific survival (DSS), and disease-free survival/recurrence-free survival (DFS/PFS) in digestive system cancers., Methods: Hazard ratios (HRs) with its 95% confidence intervals (CIs) were calculated to assess the prognostic value of AKR1B10 by using the random effects model. The STATA version 12.0 software were used to perform all the analyses., Results: Eleven articles including 1428 patients involved in this meta-analysis. The pooled analysis suggested that high AKR1B10 expression was not associated with OS (HR: 1.18; 95% CI: 0.69-2.00) and DFS/PFS (HR: 1.08, 95% CI: 0.67-1.76) in digestive system cancers. However, Further analysis revealed that high AKR1B10 expression indicated poor OS in oral squamous cell carcinomas (OSCC) (HR: 2.92, 95% CI: 1.86-4.58) and favorable DSS in hepatocellular carcinoma (HCC) (HR: 0.71, 95% CI: 0.52-0.97)., Conclusions: The prognostic value of high AKR1B10 expression varied in different types of digestive system cancers. Further studies exploring the prognostic role of AKR1B10 in digestive system cancers are needed., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Several studies on the prognostic value of microRNA 142 (miR-142) in solid tumors have reported conflicting results. Therefore, the aim of this meta-analysis was to evaluate the relationship between the miR-142 and prognosis in solid tumors. A comprehensive search for relevant studies was conducted until 10 November 2020. Studies that investigated the prognostic significance of the miR-142 in solid tumors were included. The hazard ratio and 95% confidence interval were calculated using a random-effects model. All data analyses were performed using the STATA 12.0 software (Stata Corporation, College Station, TX, U.S.A.). Twenty articles involving 2451 participants were included in the meta-analysis. The results showed that high miR-142 expression was a better predictor of overall survival (OS) (HR = 0.66, 95% CI: 0.47-0.93) and disease-free/progression-free/recurrence-free survival (DFS/PFS/RFS) (HR = 0.71, 95% CI: 0.55-0.91) compared with low miR-142 expression. MiR-142 can be used as an effective prognostic marker for patients with solid tumors. Future large prospective studies are warranted to further confirm the present findings., (© 2021 The Author(s).)

Mitochondria and chloroplast are very important organelles for organism, participating in basic life activity. Their genomes contain many repeats which can lead to a variation of genome structure. Oryza is an important genus for human beings' nutrition. Several mitochondrial and chloroplast genomes of Oryza have been sequenced, which help us to insight the distribution and evolution of the repeats in Oryza species. In this paper, we compared six mitochondrial and 13 chloroplast genomes of Oryza and found that the structures of mitochondrial genomes were more diverse than chloroplast genomes. Since repeats can change the structure of the genome, resulting in the structural diversity of the genome, we analyzed all repeats and found 31 repeats in mitochondrial and 13 repeats in chloroplast genomes. Further, we developed 21 pairs of MRS molecular markers and 12 pairs of CRS molecular markers based on mitochondrial repeats and chloroplast repeats, respectively. These molecular markers can be used to detect the repeat-mediated recombination in Oryza mitochondrial and chloroplast genomes by PCR or fluorescence quantification., Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-020-01198-6., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interests., (© The Author(s), under exclusive licence to Springer Nature B.V. part of Springer Nature 2021.)

A colorimetric assay for the determination and quantification of ascorbic acid (AA) is presented using silver nanoparticle (AgNP) single-walled carbon nanotube (AgNP/SWCNT) nanocomposites prepared using a microwave-assisted method. The AgNP/SWCNT nanocomposites possessed oxidase-like properties toward 3,3',5,5'-tetramethylbenzidine (TMB) and could catalyze the oxidation of TMB to form a blue oxidation product (λ max = 652 nm) in the absence of H 2 O 2 . AA can specifically inhibit the oxidation of TMB, resulting in a decline of the absorbance value and blue colour fading. As such, amounts of AA can be assessed easily by the unaided eye and quantitatively using an ultraviolet-visible light spectrophotometer. Under the optimal reaction conditions, this strategy showed a good linearity ranging from 0.4 μM to 5.0 μM for AA detection, and the limit of detection was 130 nM. This assay was also applied for AA measurement in vitamin C tablets and juice samples that yielded satisfactory results., (© 2020 John Wiley & Sons, Ltd.)

It has been reported that microRNA-206(miR-206) plays an important role in cancers and could be used as a prognostic biomarker. However, the results are controversial. Therefore, we summarize all available evidence and present a meta-analysis to estimate the prognostic value of miR-206 in various cancers. The relevant studies were collected by searching PubMed, EMBASE, and Web of Science databases until August 21, 2020. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were applied to explore the association between miR-206 and survival results and clinicopathologic features. Sources of heterogeneity were investigated by subgroup analysis and sensitivity analysis. Publication bias was evaluated using Egger's test. Twenty articles involving 2095 patients were included in the meta-analysis. The pooled HR showed that low miR-206 expression was significantly associated with unfavourable overall survival (OS) (HR = 2.03, 95 CI%: 1.53-2.70, P < 0.01). In addition, we found that low miR-206 expression predicted significantly negative association with tumor stage (III-IV VS. I-II) (OR = 4.20, 95% CI: 2.17-8.13, P < 0.01), lymph node status (yes VS. no) (OR = 3.58, 95%: 1.51-8.44, P = 0.004), distant metastasis (yes VS. no) (OR = 3.19, 95%: 1.07-9.50, P = 0.038), and invasion depth (T3 + T4 vs. T2 + T1) (OR = 2.43, 95%: 1.70-3.49, P < 0.01). miR-206 can be used as an effective prognostic indicator in various cancers. Further investigations are warranted to validate the present results., Competing Interests: There is no conflict of interest in the manuscript., (Copyright © 2020 Rongqiang Liu et al.)

Mineral elements play an extremely important role in human health, and are worthy of study in rice grain. Wild rice is an important gene pool for rice improvement including grain yield, disease, and pest resistance as well as mineral elements. In this study, we identified 33 quantitative trait loci (QTL) for Fe, Zn, Se, Cd, Hg, and As contents in wild rice Oryza longistaminata . Of which, 29 QTLs were the first report, and 12 QTLs were overlapped to form five clusters as qSe1/qCd1 on chromosome 1, qCd4.2/qHg4 on chromosome 4, qFe5.2/qZn5.2 on chromosome 5, qFe9/qHg9.2/qAs9.2 on chromosome 9, and qCd10/qHg10 on chromosome 10. Importantly, qSe1/qCd1 , can significantly improve the Se content while reduce the Cd content, and qFe5.2/qZn5.2 can significantly improve both the Fe and Zn contents, they were delimited to an interval about 53.8 Kb and 26.2 Kb, respectively. These QTLs detected from Oryza longistaminata not only establish the basis for subsequent gene cloning to decipher the genetic mechanism of mineral element accumulation, but also provide new genetic resource for rice quality improvement., (Copyright © 2020 Liu, Fan, Liu, Long, Yu, Yuan, Pan, Li, Li and Liu.)

Background: Several studies have investigated miR-4293 rs12220909 polymorphisms and cancer susceptibility and yielded different results. Because of this controversy, we designed a meta-analysis to assess comprehensively the association of the rs12220909 polymorphism with cancer risk., Methods: Relevant articles were collected by searching the databases of PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and WanFang. Data on rs12220909 in cancer patients and controls were extracted. Sensitivity analyses and publication bias assessments were performed., Results: Five studies with 3820 cases and 4574 controls were included in our meta-analysis. Pooled analyses showed that the rs12220909 polymorphism was not associated with cancer risk in any genetic model. (C vs G: odds ratio [OR] = 0.89, 95% confidence interval [CI] = 0.74-1.07; GC vs GG: OR = 0.83, 95% CI = 0.67-1.03; CC vs GG: OR = 1.06, 95% CI = 0.82-1.36; CC+GC vs GG: OR = 0.84, 95% CI = 0.69-1.03; CC vs GC+GG: OR = 1.10, 95% CI = 0.85-1.40)., Conclusions: Our results indicate that rs12220909 is not associated with cancer risk. Larger, well-designed multicenter studies are needed to further explore the association of miR-4293 rs12220909 polymorphism with cancer risk.

Background: Sauce braised meat products are popular in Asia, although their complicated processing may lead to potential safety risks. Especially, how hazardous compounds are formed during their preparation is still unclear. In the present study, braised chicken breasts, which are a typical Chinese sauce braised meat product, were used to investigate the formation of heterocyclic amines (HCAs) during heat treatment., Results: Precursor content (creatine and reducing sugar), HCA level and temperature were measured in different parts of the chicken breast at each processing stage. The results obtained showed that the increasing trends of total HCA content in different parts of chicken breast were not the same. Only total HCA content in the skin (4.93 ± 0.80 ng g -1 ) increased significantly after deep-frying. During braising, total HCA level in the skin was high (12.1-14.3 ng g -1 ) and relatively stable. However, total HCA content in pectoralis major muscle (3.90-7.40 ng g -1 ) and pectoralis minor muscle (1.44-5.31 ng g -1 ) was much lower than in the skin, and increased steadily with braising time., Conclusion: Braising is the main factor which affects HCA level in braised chicken. Combining the results of temperature and precursor content, a possible explanation for the large amount of HCAs in braised chicken is the gradual infiltration from reused marinade, instead of thermic generation. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

Genomic amplification of the oncogene MYCN is a major driver in the development of high-risk neuroblastoma, a pediatric cancer with poor prognosis. Given the challenge in targeting MYCN directly for therapy, we sought to identify MYCN-dependent metabolic vulnerabilities that can be targeted therapeutically. Here, we report that the gene encoding glycine decarboxylase (GLDC), which catalyzes the first and rate-limiting step in glycine breakdown with the production of the one-carbon unit 5,10-methylene-tetrahydrofolate, is a direct transcriptional target of MYCN. As a result, GLDC expression is markedly elevated in MYCN-amplified neuroblastoma tumors and cell lines. This transcriptional upregulation of GLDC expression is of functional significance, as GLDC depletion by RNA interference inhibits the proliferation and tumorigenicity of MYCN-amplified neuroblastoma cell lines by inducing G1 arrest. Metabolomic profiling reveals that GLDC knockdown disrupts purine and central carbon metabolism and reduces citrate production, leading to a decrease in the steady-state levels of cholesterol and fatty acids. Moreover, blocking purine or cholesterol synthesis recapitulates the growth-inhibitory effect of GLDC knockdown. These findings reveal a critical role of GLDC in sustaining the proliferation of neuroblastoma cells with high-level GLDC expression and suggest that MYCN amplification is a biomarker for GLDC-based therapeutic strategies against high-risk neuroblastoma.

MYCN amplification drives the development of neuronal cancers in children and adults. Given the challenge in therapeutically targeting MYCN directly, we searched for MYCN-activated metabolic pathways as potential drug targets. Here we report that neuroblastoma cells with MYCN amplification show increased transcriptional activation of the serine-glycine-one-carbon (SGOC) biosynthetic pathway and an increased dependence on this pathway for supplying glucose-derived carbon for serine and glycine synthesis. Small molecule inhibitors that block this metabolic pathway exhibit selective cytotoxicity to MYCN -amplified cell lines and xenografts by inducing metabolic stress and autophagy. Transcriptional activation of the SGOC pathway in MYCN -amplified cells requires both MYCN and ATF4, which form a positive feedback loop, with MYCN activation of ATF4 mRNA expression and ATF4 stabilization of MYCN protein by antagonizing FBXW7-mediated MYCN ubiquitination. Collectively, these findings suggest a coupled relationship between metabolic reprogramming and increased sensitivity to metabolic stress, which could be exploited as a strategy for selective cancer therapy. SIGNIFICANCE: This study identifies a MYCN-dependent metabolic vulnerability and suggests a coupled relationship between metabolic reprogramming and increased sensitivity to metabolic stress, which could be exploited for cancer therapy. See related commentary by Rodriguez Garcia and Arsenian-Henriksson, p. 3818 ., (©2019 American Association for Cancer Research.)

CD4 + CD25 + regulatory T (Treg) cells maintain the function of immune tolerance and the balance of immune cells. Defects in the number and function of Treg cells can induce the development and progression of inflammatory disease. Shikonin, the main active ingredient of Lithospermum, has anti-inflammatory and anti-tumor effects. Shikonin is also an effective drug for the treatment of psoriasis, which is a chronic inflammatory skin disease. However, the underlying mechanism is not yet clear. To evaluate the role of shikonin on the induction of Treg cells, we tested the number and function of Treg cells in vivo and in vitro. Shikonin can effectively promote the differentiation of iTreg cells by inhibiting the AKT/mTOR pathway in vitro. Moreover, in vivo, intragastrically administered shikonin effectively improved lesions in mice with imiquimod-induced psoriasis and increased the number of iTreg cells in the spleen and their secretion. Shikonin significantly increases the expression of Foxp3mRNA in skin of the psorisic mice. Therefore, we expect that shikonin can prevent the development of inflammation and treat psoriasis by regulating iTreg cells. Novel ideas for the treatment of psoriasis are also proposed.

Background and Objective: Classic vitreous biopsy, which targets the vitreous with an undiluted sample of 1 mL to 2 mL, has been used as a diagnostic analysis. Vitrectomy under air infusions have been reported to be able to extract more vitreous sample. In this study, the authors introduce a way of obtaining vitreous sample under air irrigation using 23-gauge vitrectomy and discuss the benefits and potential risks of this procedure., Patients and Methods: In this retrospective case series study, a total of 65 eyes of 65 patients with macular epiretinal membrane (ERM) or macular hole (MH) were enrolled. A vitreous biopsy was carried out with air infusion. Vitrectomy with fluid infusion was then carried out to remove the residual vitreous. Medical records of patients with macular ERM or MH were reviewed and analyzed. Clinical data, including age, sex, best-corrected visual acuity (BCVA), optical coherence tomography (OCT), axial length, presence of posterior vitreous detachment (PVD), presence of liquefication of vitreous, and refraction, were recorded and investigated. The volume of vitreous sample, visual outcome, and complications related to vitreous biopsy at 1-month follow-up were recorded and analyzed., Results: The mean of undiluted vitreous sample volume was 2.1 mL ± 0.2 mL. There were seven patients whose vitreous samples were less than 2 mL during the vitreous biopsy. The mean age of patients was 62.9 years ± 8.4 years (range: 35 years to 85 years) at diagnosis. There were 18 male and 47 female patients. At 1-month follow-up, no patient had decreased visual acuity. There was one patient who had a peripheral retinal break and was treated with photocoagulation during the operation (1.5%). The insufficient vitreous sample that may occur during the vitreous biopsy under air infusion was related to liquefication of vitreous (28.8%)., Conclusion: In summary, vitreous biopsy with air infusion is a safe and effective maneuver to harvest undiluted vitreous in patients without significant vitreous inflammation. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:365-370.]., (Copyright 2019, Zhao, Yu, Liu.)

Purpose: This study was undertaken to assess the associations between the anatomic outcomes of patients who underwent vitrectomy for rhegmatogenous retinal detachment associated with choroidal detachment (RRDCD) and their preoperative variables., Methods: A total of 175 patients with RRDCD who underwent vitrectomy in one eye were included in the analysis. The primary outcome measured was the retinal status after primary vitrectomy and at the end of follow-up., Results: The retinal reattachment rate was 72.57% after primary surgery, and the final total reattachment rate was 89.14% after follow-up. Binary logistic regression analysis identified that the retinal reattachment rate after primary vitrectomy was significantly associated with older age (odds ratio = 1.03, p = 0.02), mild proliferative vitreoretinopathy (PVR) (PVR grade C vs. PVR grades A-B: odds ratio = 0.31, p = 0.04; PVR grade D vs. PVR grades A-B: odds ratio = 0.03, p < 0.01), and intravitreal steroid treatment (odds ratio = 4.60, p = 0.02), and that the final retinal reattachment rate was independently associated with older age (odds ratio = 1.05; p = 0.01)., Conclusions: Vitrectomy is a good surgical option for RRDCD. Older age, mild preoperative PVR, and perioperative intravitreal triamcinolone acetonide injections increase the primary reattachment rates after one operation. Older age was the only independent prognostic factor for the final retinal reattachment in patients with RRDCD.

Glutaminase-1 (GLS1) is a mitochondrial enzyme found in endothelial cells (ECs) that metabolizes glutamine to glutamate and ammonia. Although glutaminolysis modulates the function of human umbilical vein ECs, it is not known whether these findings extend to human ECs beyond the fetal circulation. Furthermore, the molecular mechanism by which GLS1 regulates EC function is not defined. In this study, we show that the absence of glutamine in the culture media or the inhibition of GLS1 activity or expression blocked the proliferation and migration of ECs derived from the human umbilical vein, the human aorta, and the human microvasculature. GLS1 inhibition arrested ECs in the G 0 /G 1 phase of the cell cycle and this was associated with a significant decline in cyclin A expression. Restoration of cyclin A expression via adenoviral-mediated gene transfer improved the proliferative, but not the migratory, response of GLS1-inhibited ECs. Glutamine deprivation or GLS1 inhibition also stimulated the production of reactive oxygen species and this was associated with a marked decline in heme oxygenase-1 (HO-1) expression. GLS1 inhibition also sensitized ECs to the cytotoxic effect of hydrogen peroxide and this was prevented by the overexpression of HO-1. In conclusion, the metabolism of glutamine by GLS1 promotes human EC proliferation, migration, and survival irrespective of the vascular source. While cyclin A contributes to the proliferative action of GLS1, HO-1 mediates its pro-survival effect. These results identify GLS1 as a promising therapeutic target in treating diseases associated with aberrant EC proliferation, migration, and viability., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Tetraspanin CD151 has been identified as a tumor promoter, which is upregulated in various malignant cell types. However, the function of CD151 and its underlying mechanism in renal cell carcinoma is still unknown. In this study, we detected the expression of CD151 in RCC cells and tissues and explored its regulatory mechanism. We found that CD151 was upregulated in renal cell carcinoma tissues and cells and its expression was significantly associated with tumor stage (p=0.019) and survival (p=0.001) by analyzing tissue microarrays. After silencing of CD151 via lentivirus vector in Caki-1 and Caki-2 cells, reduced ability of migration and invasion were detected with downregulation of CD151. The opposite results were observed in cells with CD151 overexpression. Furthermore, western blotting was performed to investigate the influence of CD151 on epithelial-to-mesenchymal transition, matrix metalloproteinase 9 and TGF-β1/Smad signaling pathway in RCC. Subsequently, upregulating the protein level of transforming growth factor-β1 in cells with silencing of CD151 could rescue the malignant behaviors inhibited, which indicated that CD151 may play its promoting role in RCC partially by stimulating the expression of TGF-β1. Conclusively, CD151 might exhibit a prominent role in migration and invasion of RCC cells via activating TGF-β1/Smad signaling pathway., Competing Interests: CONFLICTS OF INTEREST All authors have read and approved the final manuscript, and do not have a commercial or other association that might pose a conflict of interest.

Background: Currently, the standard treatment for renal pelvis carcinoma is radical nephroureterectomy with bladder cuff excision. To describe the feasibility of retroperitoneal laparoscopic partial nephrectomy with segmental renal artery clamping for cancer of renal pelvis, we report this special case for the first time., Case Presentation: A 67-year-old woman received this operation. Preoperative ureteroscopy revealed a papillary neoplasm with a pedicle in the upper calyx of the left kidney. After entering the retroperitoneal space and dissociating the renal artery and renal vein, the target artery was clamped beyond the final bifurcation before entering the parenchyma. After incision of the left renal parenchyma and exposure of the upper calyceal neck, the tumor was found confined to the upper calyx. Thereafter, the renal calyx and parenchyma were sutured successively after complete resection of the neoplasm. Postoperative pathological examination confirmed that the Grade I papillary carcinoma was confined to the mucosal layer. Thus far, there is no evidence of recurrence during the follow-up period for more than 42 months after surgery., Conclusions: Retroperitoneal laparoscopic partial nephrectomy with segmental renal artery clamping of the kidney provides a feasible treatment modality for noninvasive tumors that are limited to the calyx.